Erectile dysfunction is a common illness that is estimated to affect 10 to 30 million men in the United States (Feldman, et al. Joumal of Clinical Epidemiology 47.5 (1994) 457-67; Anonymous, International Journal of Impotence Research 5.4 (1993) 181-284). Among the primary disease-related causes of erectile dysfunction are atherosclerosis, diabetes, aging, hypertension and antihypertensive medication, chronic renal disease, pelvic surgery and radiation therapy, and psychological anxiety (Feldman, et al. Journal of Clinical Epidemiology 47.5 (1994) 457-67). Direct cures for the vascular ravages of these manifold and multifaceted disease states are unlikely to occur in the near future, and thus, the last decade has witnessed the development of several treatment modalities to directly restore diminished erectile capacity. However, all currently available therapies are either non-specific (hormonal therapy), of limited overall success (e.g., vacuum erection devices), invasive (e.g., intracorporal injection therapy) or non-reversible and expensive (e.g., penile prosthetic implant surgery). Despite these therapeutic limitations the recent FDA approval of Caverject (prostaglandin E.sub.1) for the intracavernous treatment of erectile dysfunction represents a major step forward. In essence, this act of the Federal Government has resulted in both the formal recognition of the medical nature of the problem, and furthermore, legitimized its clinical treatment.
Recent changes in contemporary cultural patterns in the United States have allowed for a free and more open public discussion of sex and sexual dysfunction. This cultural trend has both highlighted the magnitude of the problem, and simultaneously emphasized the need for improved clinical treatment of erectile dysfunction. The recent deluge of advertising and media activity related to the discussion and treatment of the problem has made men, and their sexual partners more aware that erectile dysfunction is a common problem with legitimate (federally approved) clinical treatments available. This combination of events will continue to promote even larger numbers of men to seek treatment for impotence from their physicians during the next decade. There is thus a need for a better understanding the impact of age and disease on human erection through the study of the function of the corporal and arterial smooth muscle at the whole tissue, cellular, and most recently at the subcellular level. Also needed is a research strategy that will enable the direct translation of the results of laboratory work to the clinical environment, ensuring that new treatments for organic erectile dysfunction will be more cost effective, of greater efficacy and with fewer side effects.
Studies have documented that altered corporal smooth muscle tone, resulting in either heightened contractility or impaired relaxation, is a proximal cause of erectile dysfunction in a large proportion of impotent men. These studies have further indicated that complete relaxation of the corporal smooth muscle is both a necessary and sufficient condition to restore erectile potency, unless severe arterial disease or congenital structural abnormalities exist; the latter is true in a minority of patients. The FDA approval of the intracavernous injection of the smooth muscle relaxant PGE.sub.1 verifies the validity of this supposition.
As described above, the critical role played by the corporal smooth muscle cells in erectile function makes them a excellent target for molecular intervention in the treatment of erectile dysfunction. Previous efforts have focused on techniques for gene transfer into vascular smooth muscle cells as a basis for the potential therapy of several cardiovascular diseases. Among these are atherosclerosis, vasculitis and restenosis after balloon angioplasty. These initial studies have provided important information on the efficiency and persistence of gene transfer methods in smooth muscle cells (Finkel, et al. FASEB Journal 9 (1995) 843-51).
Thus, because erectile dysfunction is largely caused by altered smooth muscle tone, a method of gene therapy which targets the genes involved in the alteration of smooth muscle tone is extremely desirable. Further, of critical importance with respect to all in vivo gene therapy approaches is the percentage of target cells that must be affected, and the relative efficiency of affecting only the desired cell type(s) to see a physiologically relevant therapeutic effect. Accordingly, there is a need for a method of gene therapy wherein only a small number of cells would need to be genetically modified to affect global changes in tissue function. Finally, a successful method of gene therapy for alleviating erectile dysfunction is in great demand as it would be a preferred alternative to currently used methods.